Knee Osteoarthritis (KOA) is a condition that causes pain and stiffness in the knee joint. It affects many older adults and is a big health problem worldwide. Surgery is not always the best choice because it can still leave people in pain. This study aims to find better ways to treat KOA without surgery or opioids, which are strong pain medicines.

The study will have two phases. In Phase 1, researchers will try different non-opioid medicines and behavioral treatments. If more help is needed, Phase 2 will offer other medical procedures. The study will help understand which treatment works best for different people.

• The study involves two phases with different treatments.
• Participants should expect to undergo a randomized controlled trial.
• Women who are pregnant or plan to become pregnant should not participate.

To join the study, you must be over 18, have knee pain, and meet specific health criteria. People with certain health conditions or who have had specific knee treatments recently might not be eligible. Participants are expected to use reliable birth control methods if of childbearing potential.